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Structure of 4-(Chlorosulfonyl)benzoic acid
CAS No.: 10130-89-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 10130-89-9 |
Formula : | C7H5ClO4S |
M.W : | 220.63 |
SMILES Code : | OC(=O)C1=CC=C(C=C1)S(Cl)(=O)=O |
MDL No. : | MFCD00007448 |
InChI Key : | PTCSSXYPZOFISK-UHFFFAOYSA-N |
Pubchem ID : | 82385 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
79.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.33 |
Solubility | 1.03 mg/ml ; 0.00467 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.73 |
Solubility | 0.409 mg/ml ; 0.00185 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.32 |
Solubility | 1.06 mg/ml ; 0.00479 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.62 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.47 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 183 4-(2-Methoxy-5-phenylcarbamoyl-phenylsulfamoyl)-benzoic acid The title compound has been made using the procedure of Example 121, but using 3-amino-4-methoxy-N-phenyl benzamide and 4-carboxybenzenesulfonyl chloride as starting materials, which are commercially available from Aldrich; m.p. 212-214 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With pyridine; In dichloromethane; at 20℃; for 12.0h; | 4-(Chlorosulfonyl)benzoic acid (25.0 g, 113 mmol) and <strong>[191478-99-6]methyl 4-amino-2,6-difluorobenzoate</strong> (19.0 g, 101 mmol) were dissolved in methylene chloride (500 ml), and pyridine (25.0 ml, 285 mmol) was added thereto, followed by stirring at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure. The obtained residue was diluted with water, and then the pH was adjusted to 1.0 by adding 6 N hydrochloric acid. The precipitated solid was filtered, and washed with water. The obtained solid was resuspended in water, and washed with a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate (100 ml×2). The pH of the obtained aqueous layer was adjusted to 6.0 by adding 6 N hydrochloric acid thereto, followed by extraction with ethyl acetate (100 ml×2). The extraction liquids were combined, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. Then, the solvent was removed to obtain the title compound (15.0 g, 36%). [0213] 1H NMR (d-DMSO, 400 MHz): delta 11.50 (s, 1H), 8.14 (d, J=8.4 Hz, 2H), 8.01 (d, J=8.4 Hz, 2H), 6.67 (d, J=10.4 Hz, 2H), 3.87 (s, 3H); MS (ESI) m/z 372 (M+H)+ |
36% | With pyridine; In dichloromethane; at 20℃; for 12.0h; | (Step 1) 4-([3,5-Difluoro-4-(methoxycarbonyl)phenyl]amino}sulfonyl)benzoic acid (0430) (0431) 4-(Chlorosulfonyl)benzoic acid (25.0 g, 113 mmol) and <strong>[191478-99-6]methyl 4-amino-2,6-difluorobenzoate</strong> (19.0 g, 101 mmol) were dissolved in methylene chloride (500 ml), pyridine (25.0 ml, 285 mmol) was added thereto, and the resulting mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, the obtained residue was diluted with water, a 6 N aqueous solution of hydrochloric acid was added for adjustment of the pH to 1.0, and the precipitated solid was filtered and washed with water. The obtained solid was suspended in water again, washed with a saturated aqueous solution of sodium hydrogen carbonate, and then extracted with ethyl acetate (100 ml×2). A 6 N aqueous solution of hydrochloric acid was added to the obtained aqueous layer for adjustment of the pH to 6.0, and ethyl acetate was added (100 ml×2) for extraction. The extracts were combined, washed with a saturated saline solution, dried over anhydrous sodium sulfate, and then the solvent was removed to obtain the title compound (15.0 g, 36%). (0432) 1H NMR (d-DMSO, 400 MHz): delta 11.50 (s, 1H), 8.14 (d, J=8.4 Hz, H), 8.01 (d, J=8.4 Hz, 2H), 6.67 (d, J=10.4 Hz, 2H), 3.87 (s, 3H); MS (ESI) m/z 372 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine; In tetrahydrofuran; dichloromethane; at 0 - 20℃; | General procedure: 2-(Piperazin-1-yl)benzazolylderivatives 5a-d (1 equivalent) and triethylamine (1.5 equivalents) were dissolved in25 mL dry CH2Cl2 and cooled to 0C in an ice salt bath. Then the required 3 or 4-Chloro-sulfonylbenzoicacid (1.1 equivalents) dissolved in 15 mL dry THF was added dropwise. After theaddition, the reaction mixture was stirred at 0C for a further 1 h and then allowed to warm toroom temperature and the course of the reaction followed by TLC (CH2Cl2/MeOH/konz. NH3:898/100/2). After indicating the end of the reaction, the mixture was evaporated to dryness, the residue was dissolved in dist. water and made slightly acidic (pH 6) with glacial acetic acid andstirred for about 30 mins. The solid formed was filtered by suction, washed with water andthen with petrol ether. The product was recrystallized from the appropriate solvent; the precipitateformed was filtered under suction and dried at 60C under high vacuum. |
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